Experimental animals administered with high single doses of cyclophosphamide (CY) have low cytotoxic T-cell (CTL) activity against both allogeneic and syngeneic tumor cells using in vitro and in vivo assay systems. This low CTL activity can be restored to normal levels by exposure of the CRL procursors to T-cell derived helper factor. The aims of this proposal are to determine the optimal conditions for delivery of this helper factor in vivo to mice bearing transplantable and syngeneic spontaneous tumors after they have received therapeutic doses of CY. The helper factor will be injected chronically intramuscularly, infused by means of mini-osmotic pumps or delivered by means of liposomes. We will study the kinetics of CTL development in tumor bearing mice after one or several injections of CY together with the administration of helper factor in vivo. CTL activity of mice bearing syngeneic or allogeneic tumors and administered with high dose CY, will be monitored over an extended period of time with and without the administration of helper factor. In addition, mice bearing transplantable or spontaneous tumors will be injected with therapeutic doses of CY together with helper factor and tumor growth, median survival time and per-cent cures will be monitored. We believe that certain naturally occuring immunological modifiers such as T-cell derived helper factor are eliminated by immunosuppressive, anto-cancer agents. These modifiers may be supplied exogenously after chemotherapy to rescue a specific arm of the immune system. We show in this proposal that CTL responses can be restored to normal levels after CY therapy by the exogenous administration of helper factor in vivo. This proposal outlines several protocols for the delivery of helper factor in vivo such that the CTL response is restored to normal levels and the host's immune defense mechanisms may be more properly aligned to eliminate residual antigenic tumor cells, and of equal importance, pathological infections.